P63 gene mutations and human developmental syndromes

Am J Med Genet. 2002 Oct 15;112(3):284-90. doi: 10.1002/ajmg.10778.


The P63 gene is a recently discovered member of the p53 family. While P53 is ubiquitously expressed, p63 is expressed specifically in embryonic ectoderm and in the basal regenerative layers of epithelial tissues in the adult. Complete abrogation of P63 gene function in an animal model points to the relevance of P63 for the proper development of ectodermally derived tissues. The p63 knockout mouse dies at birth and has truncation of the limbs, as well as absence of epidermis, prostate, breast, and urothelial tissues, apparently reflecting ectodermal stem cell loss. A number of dominant human syndromes have been mapped to chromosome 3q27 and ultimately to mutations in the p63 gene. These syndromes have abnormal limb development and/or ectodermal dysplasia and include ectrodactyly, ectodermal dysplasia, clefting syndrome; ankyloblepharon, ectodermal dysplasia, clefting syndrome; acro-dermato-ungual-lacrimal-tooth syndrome; limb-mammary syndrome; as well as nonsyndromic split hand/foot malformation. The pattern of heterozygous mutations is distinct for each of these syndromes. Consistent with this syndrome-specific mutational pattern, the functional consequences of mutations on the p63 proteins also vary, invoking dominant-negative and gain-of-function mechanisms rather than a simple loss of function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Animals
  • Breast / abnormalities
  • DNA-Binding Proteins
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Limb Deformities, Congenital / genetics
  • Male
  • Membrane Proteins*
  • Mice
  • Mice, Knockout
  • Mutation*
  • Phosphoproteins / genetics*
  • Syndrome
  • Trans-Activators / genetics*
  • Transcription Factors
  • Tumor Suppressor Proteins


  • CKAP4 protein, human
  • DNA-Binding Proteins
  • Membrane Proteins
  • Phosphoproteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Trp63 protein, mouse
  • Tumor Suppressor Proteins